Active Voice: Aggravation of Exercise-Induced Intestinal Injury by Ibuprofen in Athletes

By Kim van Wijck, M.D.

Viewpoints presented in SMB commentaries reflect the opinions of the authors and do not necessarily reflect positions or policies of ACSM.

Dr. Kim van Wijck is a surgical resident at the Department of General Surgery at ORBIS Medical Center, Maastricht, the Netherlands. Before the start of her clinical work, she was a researcher at Maastricht University Medical Center and Top Institute Food and Nutrition, the Netherlands. Her scientific interests relate to the understanding of physiological and pathophysiological changes in splanchnic perfusion in man. The latter, including the role of strenuous physical exercise on splanchnic perfusion and gastrointestinal wellbeing, is a part of her upcoming Ph.D. thesis.

This commentary presents Dr. Van Wijck’s views on the topic of a related research article which she and her colleagues published in the December 2012 issue of
Medicine and Science in Sports and Exercise®.

Pain killers are commonly used by athletes to prevent anticipated exercise-related pain. It is generally assumed that pain killers improve athletic performance by enabling more frequent and more intensive exercise. While there is no evidence that pain killers actually improve performance, evidence is accumulating that non-steroidal anti-inflammatory drugs (NSAIDs), especially, exert hazardous effects on the cardiovascular and gastrointestinal system.

Recent studies have demonstrated an increase in cardiovascular events associated with the use of NSAIDs, showing an elevated risk of approximately 25% for non-fatal myocardial infarction. In addition, NSAIDs have been described to cause gastrointestinal (GI) complications such as mucosal ulceration, bleeding and perforation. Especially long-term users of NSAIDs were reported to be at risk. However, mucosal ulceration has also been demonstrated in athletes using NSAIDs after completion of a long-distance run.

In our previous study, we demonstrated that exercise reduces the perfusion of the gastrointestinal system, leading to hypoperfusion of the gut. Such a decrease in intestinal perfusion is the result of a redistribution of the blood flow during exercise, directing the blood toward the active muscles, heart and lungs, away from the gastrointestinal system. We demonstrated that the resulting exercise-related intestinal hypoperfusion leads to small intestinal injury and temporary loss of gut barrier function in otherwise healthy individuals.

NSAIDs have been described to impair local perfusion due to inhibition of the enzyme cyclo-oxygenase (COX)-1 and reduced production of local nitric oxide via regulation of the NF-kappa-B pathway. In addition, NSAIDs inhibit COX-2 production, thereby compromising immunomodulation. We hypothesized that the use of NSAIDs in combination with strenuous exercise causes profound intestinal injury. Our recent study in MSSE was conducted to examine whether the short-term use of the NSAID ibuprofen (two single doses of 400 mg each) prior to one hour of strenuous exercise aggravates exercise-induced small intestinal injury in healthy, young athletes.

The athletes were studied on four different occasions: (1) ibuprofen + cycling; (2) cycling; (3) ibuprofen + rest; and (4) rest. To assess small intestinal injury, plasma levels of intestinal fatty acid binding protein (I-FABP) were measured, while urinary excretion of orally ingested multi-sugar test probes was determined using liquid chromatography and mass spectrometry to assess GI barrier function. Indeed, the intake of ibuprofen prior to one hour of exercise aggravated the exercise-induced small intestinal injury, reflected by highest I-FABP levels in the ibuprofen + cycling treatment. In line with these observations, loss of gut barrier function was most pronounced in case of ibuprofen + cycling.

Taken together, these data clearly demonstrate that ibuprofen prior to exercise aggravates exercise-induced small intestinal injury and gut barrier dysfunction in healthy individuals. Since athletes often use higher doses of NSAIDs and exercise for more than one hour, we expect the intestinal compromise of NSAIDs plus exercise to be even more pronounced in daily practice. We conclude that NSAID consumption by athletes is not harmless and should be strongly discouraged, especially if used for anticipated pain.